HCMV is beta-herpesvirus and is maintained for the lifetime of the infected host as a persistent infection. Historically, infection with this virus poes a threat to the immunocompromised, including patients with AIDS and those receiving organ transplants. The virus is ubiquitous and most adults are infected by age 40. In the healthy host, the acute phase of infection is self-limiting and the virus establishes a latent infection that can be reactivated in response to a variety of cellular stresses. Cells of the myeloid lineage are the reservoir for the virus. HCMV infection induces chronic inflammation; thus, the role of HCMV persistence in the pathology of diseases with inflammatory components, such as cardiovascular disease and cancer, is the focus of many studies. HCMV acquires a lipid envelope in the cytoplasm of infected cells but little is known about the effects of infection on lipid metabolism and trafficking. We have previously shown that infection blocked the conversion of THP-1 derived macrophages into lipid-laden foam cells in response to treatment with oxidized LDL. Subsequently, we observed that the virus inhibited the ability of cells to bind the lipoprotein, an interaction mediated by scavenger receptors on the cell surface. Our studies indicate that infection likely disrupts lipid raft microdomains on the plasma membrane and thereby inhibits scavenger receptor functions. The ultimate goal of this project is to understand the mechanisms that control lipid raft stability and scavenger receptor function in HCMV- infected cells. To accomplish this goal we will investigate changes in plasma membrane composition after infection and determine the roles of viperin, ABCA1, and SR-BI in regulation of receptor activity through their effects on lipid raft stability. The present studies will provide the foundation for future work.